Abstract
N-methyl bromide of lidocaine (QX-314) is a potential local anaesthetic with compromised penetration through cell membranes due to its obligated positive charge. Liposomes have been widely used for drug delivery with promising efficacy and safety. Therefore we investigated the local anaesthetic effects and tissue reactions of QX-314 in combination with anionic, cationic or neutral liposomes in rat sciatic nerve block model, and explored the effects of these liposomes on cellular entry of QX-314 in human embryonic kidney 293 cells. The results demonstrated that anionic liposomes substantially prolonged the duration of sensory (25.7 ± 8.3 h) and motor (41.4 ± 6.1 h) blocks of QX-314, while cationic and neutral ones had little effects. Tissue reactions from QX-314 with anionic liposomes were similar to those with commonly used local anaesthetic bupivacaine. Consistent with in vivo results, the anionic liposomes produced the greatest promotion of cellular entry of QX-314 in a time-dependent manner. In conclusion, ultra-long lasting nerve blocks were achieved by a mixture of QX-314 and anionic liposomes with a satisfactory safety profile, indicating a potential approach to improve postoperative pain management. The liposome-induced enhancement in cellular uptake of QX-314 may underlie the in vivo effects.